Pregnancy Complications from Herceptin, PERJETA, and KADCYLA

Herceptin: Taking Herceptin during pregnancy can result in reduced amniotic fluid (oligohydramnios), in some cases complicated by incomplete development of the lungs (pulmonary hypoplasia), and death of the newborn child.

PERJETA: Exposure to PERJETA can result in embryo-fetal death and birth defects. Studies in animals have resulted in reduced amniotic fluid (oligohydramnios), delayed development of the kidneys, and death.

KADCYLA: KADCYLA can cause harm to the unborn child when administered to a pregnant woman. There are no adequate and well-controlled studies of KADCYLA in pregnant women, and no reproductive and developmental toxicology studies have been conducted. Nevertheless, the two components of KADCYLA (trastuzumab and DM1) are known or suspected to cause fetal harm or death when given to a pregnant woman.

Treatment with trastuzumab, the antibody component of KADCYLA, during pregnancy in the postmarketing setting has resulted in reduced amniotic fluid (oligohydramnios), in some cases associated with fatal pulmonary hypoplasia, skeletal abnormalities, and death of the newborn child. DM1, the cytotoxic component of KADCYLA, can be expected to cause embryo-fetal toxicity based on how it works.

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A registry representative will be in touch with you to finalize enrollment details and respond to any question you may have.

What is the MotHER Pregnancy Registry?

What is the MotHER Pregnancy Registry?

The MotHER Pregnancy Registry* was established for women who have taken Herceptin® (trastuzumab), PERJETA® (pertuzumab), or KADCYLA® (ado-trastuzumab emtansine) for breast cancer during pregnancy or within seven months of becoming pregnant. The goal is to learn about the health of these women and their babies.

Who is Herceptin for?

Adjuvant Breast Cancer

Herceptin is approved for the treatment of early-stage breast cancer that is HumanEpidermal growth factor Receptor 2-positive (HER2+) and has spread into the lymph nodes, or is HER2+ and has not spread into the lymph nodes. If it has not spread into the lymph nodes, the cancer needs to be estrogen receptor/progesterone receptor (ER/PR)-negative or have one high risk feature.* Herceptin can be used in several different ways:

As part of a treatment course including the chemotherapy drugs Adriamycin® (doxorubicin), Cytoxan® (cyclophosphamide), and either Taxol® (paclitaxel) or Taxotere® (docetaxel). This treatment course is known as "AC→TH."

With the chemotherapy drugs Taxotere and Paraplatin® (carboplatin). This treatment course is known as "TCH."

Alone after treatment with multiple other therapies, including an anthracycline (Adriamycin)-based therapy (a type of chemotherapy).

*High risk is defined as ER/PR-positive with one of the following features: tumor size >2 cm, age <35 years, or tumor grade 2 or 3. Adriamycin is a registered trademark of Pharmacia, Inc. Cytoxan, Taxol, and Paraplatin are registered trademarks of Bristol-Myers Squibb Company. Taxotere is a registered trademark of sanofi-aventis U.S. LLC.

Metastatic Breast Cancer

Herceptin has 2 approved uses in metastatic breast cancer:

Herceptin in combination with the chemotherapy drug Taxol® (paclitaxel) is approved for the first line treatment of Human Epidermal growth factor Receptor 2-positive (HER2+) metastatic breast cancer.

Herceptin alone is approved for the treatment of HER2+ breast cancer in patients who have received one or more chemotherapy courses for metastatic disease.

Taxol is a registered trademark of Bristol-Myers Squibb Company.

Gastric Cancer

Herceptin is approved, in combination with chemotherapy (cisplatin and either capecitabine or 5-fluorouracil), for the treatment of HER2+ metastatic cancer of the stomach or gastroesophageal junction (where the esophagus meets the stomach) in patients who have not received prior treatment for their metastatic disease.

What are the possible Serious Side Effects of Herceptin?

Heart Problems

Herceptin treatment can result in heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure). The risk and seriousness of these heart problems were highest in people who received both Herceptin and a certain type of chemotherapy (anthracycline). One patient died in an adjuvant (early) breast cancer trial of significantly weakened heart muscle.

Herceptin can cause serious heart problems, including:

A decline in heart function

Irregular heartbeats

High blood pressure

Serious heart attack

Death

Your doctor will stop Herceptin therapy if you have weakening of the heart muscle or changes in the heart muscle structure.

Monitoring the Heart

Your doctor will evaluate your heart function before and during treatment. For adjuvant breast cancer therapy, your doctor will also evaluate heart function after the end of treatment.

Your doctor may run tests, such as an echocardiogram or a MUGA scan, and will review your health history to see how well the heart muscle is working.

If you are taking Herceptin and have stopped treatment temporarily because of significant heart problems, your doctor should monitor your heart health more frequently.

Infusion Reactions

Some patients have had serious infusion reactions and lung problems; infusion reactions leading to death have been reported.

Symptoms usually happen during or within 24 hours of taking Herceptin.

Your infusion should be temporarily stopped if you experience shortness of breath or very low blood pressure.

Your doctor should monitor you until these symptoms completely go away.

Your doctor may have you completely stop Herceptin treatment if you have:

A severe allergic reaction

Swelling

Lung problems

Swelling of the lungs

Severe shortness of breath

Infusion reaction symptoms consist of:

Fever and chills

Nausea

Vomiting

Pain (in some cases at tumor sites)

Headache

Dizziness

Shortness of breath

Very low blood pressure

Rash

Lack of energy and strength

Pregnancy

Herceptin can cause harm to the fetus (unborn baby), in some cases death to the fetus, when taken by a pregnant woman.

You should use effective birth control methods while receiving Herceptin and for at least 6 months after you finish taking Herceptin.

Nursing mothers taking Herceptin may want to stop nursing or stop Herceptin, depending on the importance of the drug to the mother.

Taking Herceptin Can Result in Serious and Potentially Deadly Lung Problems, Including:

A severe shortness of breath

Fluid in or around the lungs

Weakening of the valve between the heart and the lungs

Too little oxygen in the body

Swelling of the lungs

Scarring of the lungs

Problems like these may occur after an infusion reaction. If you have trouble breathing at rest due to existing lung disease, or large lung tumors appear, you may have more serious lung problems. Your doctor should stop Herceptin if you experience lung problems.

What is the Additional Important Safety Information associated with Herceptin?

Worsening of Low White Blood Cell Counts Due to Chemotherapy

Worsening of low white blood cell counts to serious and life-threatening levels and associated fever were higher in patients taking Herceptin in combination with chemotherapy when compared with those who received chemotherapy alone. The likelihood that a patient will die from infection was similar among patients who received Herceptin and those who did not.

HER2 Testing

You must have a HER2 test to determine if your cancer is HER2-positive before taking Herceptin, as benefit has only been shown in patients whose tumors are HER2-positive.

What Are the Most Common Side Effects Associated with Herceptin?

The most common side effects associated with Herceptin in patients with metastatic stomach cancer are:

The most common side effects associated with Herceptin in patients with breast cancer are:

Low white blood cell counts

Diarrhea

Feeling tired

Low red blood cell counts

Swelling of the mouth lining

Weight loss

Upper respiratory tract infections

Fever

Low platelet counts

Swelling of the mucous membranes

Swelling of the nose and throat

Change in taste

Fever

Nausea

Vomiting

Infusion reactions

Diarrhea

Infections

Increased cough

Headache

Feeling tired

Shortness of breath

Rash

Low white and red blood cell counts

Muscle pain

What should I look for when I'm on Herceptin therapy, and what symptoms should I immediately report to my doctor?

Patient Counseling Information

You should contact your doctor immediately for any of the following:

New onset or worsening shortness of breath

Cough

Swelling of the ankles/legs

Swelling of the face

Palpitations

Weight gain of more than 5 pounds in 24 hours

Dizziness or loss of consciousness

If you are pregnant or of childbearing potential, you should know that Herceptin exposure can result in harm to the fetus (unborn baby).

You should use effective birth control methods during treatment and for a minimum of six months following Herceptin.

If you are nursing your baby, you should stop taking Herceptin or stop nursing.

Who is Herceptin for?

Adjuvant Breast Cancer

Herceptin is approved for the treatment of early-stage breast cancer that is Human Epidermal growth factor Receptor 2-positive (HER2+) and has spread into the lymph nodes, or is HER2+ and has not spread into the lymph nodes. If it has not spread into the lymph nodes, the cancer needs to be estrogen receptor/progesterone receptor (ER/PR)-negative or have one high-risk feature.* Herceptin can be used in several different ways:

As part of a treatment course including the chemotherapy drugs Adriamycin® (doxorubicin), Cytoxan ® (cyclophosphamide), and either Taxol ® (paclitaxel) or Taxotere ® (docetaxel). This treatment course is known as "AC TH."

With the chemotherapy drugs Taxotere and Paraplatin ® (carboplatin). This treatment course is known as “TCH.”

Alone after treatment with multiple other therapies, including an anthracycline (Adriamycin)-based therapy (a type of chemotherapy).

*

High-risk is defined as ER/PR-positive with one of the following features: tumor size > 2 cm, age < 35 years, or tumor grade 2 or 3.

Adriamycin is a registered trademark of Pharmacia, Inc. Cytoxan, Taxol, and Paraplatin are registered trademarks of Bristol-Myers Squibb Company. Taxotere is a registered trademark of sanofi-aventis U.S. LLC.

Herceptin alone is approved for the treatment of HER2+ breast cancer in patients who have received one or more chemotherapy courses for metastatic disease.

Taxol is a registered trademark of Bristol-Myers Squibb Company.

Metastatic Gastric Cancer

Herceptin is approved, in combination with chemotherapy (cisplatin and either capecitabine or 5-fluorouracil), for the treatment of HER2+ metastatic cancer of the stomach or gastroesophageal junction (where the esophagus meets the stomach) in patients who have not received prior treatment for their metastatic disease.

What possible Serious Side Effects and Additional Important Safety Information should I know about Herceptin?

Heart Problems and Monitoring

Herceptin treatment can result in heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure). The risk and seriousness of these heart problems were highest in people who received both Herceptin and a certain type of chemotherapy (anthracycline). One patient died in an adjuvant (early) breast cancer trial of significantly weakened heart muscle.

Your doctor will evaluate your heart function before and during treatment. For adjuvant breast cancer therapy, your doctor will also evaluate heart function after the end of treatment. Your doctor will stop Herceptin therapy if you have weakening of the heart muscle or changes in the heart muscle structure.

If you are taking Herceptin and have stopped treatment temporarily because of significant heart problems, your doctor should monitor your heart health more frequently.

Infusion Reactions and Lung Problems

Some patients have had serious infusion reactions and lung problems; infusion reactions leading to death have been reported.

Symptoms usually happen during or within 24 hours of taking Herceptin.

Your infusion should be temporarily stopped if you experience shortness of breath or very low blood pressure.

Your doctor should monitor you until these symptoms completely go away.

Your doctor may have you completely stop Herceptin treatment if you have:

A severe allergic reaction

Swelling

Lung problems

Swelling of the lungs

Severe shortness of breath

Pregnancy

Herceptin can cause harm to the fetus (unborn baby), in some cases death to the fetus, when taken by a pregnant woman.

Worsening of Low White Blood Cell Counts Due to Chemotherapy

Worsening of low white blood cell counts to serious and life-threatening levels and associated fever were higher in patients taking Herceptin in combination with chemotherapy when compared with those who received chemotherapy alone.

HER2 Testing

You must have a HER2 test to determine if your cancer is HER2-positive before taking Herceptin, as benefit has only been shown in patients whose tumors are HER2-positive.

Most Common Side Effects

The most common side effects associated with Herceptin in patients with metastatic stomach cancer are:

Low white blood cell counts

Diarrhea

Feeling tired

Low red blood cell counts

Swelling of the mouth lining

Weight loss

Upper respiratory tract infections

Fever

Low platelet counts

Swelling of the mucous membranes

Swelling of the nose and throat

Change in taste

The most common side effects associated with Herceptin in patients with breast cancer are:

Fever

Nausea

Vomiting

Infusion reactions

Diarrhea

Infections

Increased cough

Headache

Feeling tired

Shortness of breath

Rash

Low white and red blood cell counts

Muscle pain

Patient Counseling Information

You should contact your doctor immediately for any of the following:

New onset or worsening shortness of breath

Cough

Swelling of the ankles/legs

Swelling of the face

Palpitations

Weight gain of more than 5 pounds in 24 hours

Dizziness or loss of consciousness

If you are pregnant or of childbearing potential, you should know that Herceptin exposure can result in harm to the fetus (unborn baby).

You should use effective birth control methods during treatment and for a minimum of six months following Herceptin.

If you are nursing your baby, you should stop taking Herceptin or stop nursing.

What does PERJETA treat?

PERJETA® (pertuzumab) is approved for use in combination with Herceptin® (trastuzumab) and docetaxel in people who have HER2-positive breast cancer that has spread to different parts of the body (metastatic) and who have not received anti-HER2 therapy or chemotherapy for metastatic breast cancer.

PERJETA® (pertuzumab) is approved for use prior to surgery in combination with Herceptin®(trastuzumab) and docetaxel in people with HER2-positive, locally advanced, inflammatory, or early stage (tumor is greater than 2 cm in diameter or node positive) breast cancer. PERJETA should be used as part of a complete treatment regimen for early stage breast cancer. This use of PERJETA is based on an improvement in the percentage of patients whose cancer shrinks or disappears after treatment. Currently, no data have shown whether or not treatment with PERJETA prior to surgery improves survival.

The safety of PERJETA in combination with doxorubicin-containing regimens has not been established

The safety of PERJETA administered for greater than 6 cycles for early-stage breast cancer has not been established

Important Safety Information

What should I know about side effects with PERJETA?

Not all people have serious side effects; however, side effects with PERJETA therapy are common. It is important to know what side effects may happen and what symptoms you should watch for

Your doctor may stop treatment if serious side effects happen. Be sure to contact your healthcare team right away if you have questions or are worried about any side effects

What are the most serious side effects?

PERJETA may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure).

Your doctor may run tests to monitor your heart function before and during treatment with PERJETA

Based on test results your doctor may hold or discontinue treatment with PERJETA

Receiving PERJETA during pregnancy can result in the death of an unborn baby and birth defects.

Birth control should be used while receiving PERJETA and for 6 months after your last dose of PERJETA. If you are a mother who is breastfeeding, you should talk with your doctor about either stopping breastfeeding or stopping PERJETA

If you think you may be pregnant, you should contact your healthcare provider immediately

If you are exposed to PERJETA during pregnancy, you are encouraged to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720.

What are other possible serious side effects?

PERJETA should not be used in patients who are allergic to pertuzumab or to any of the ingredients in PERJETA

Infusion-related reactions: PERJETA is a medicine that is delivered into a vein through a needle. This process can cause reactions known as infusion-related reactions. The most common infusion-related reactions when receiving PERJETA, Herceptin, and docetaxel were feeling tired, abnormal or altered taste, allergic reactions, muscle pain, and vomiting. The most common infusion-related reactions when receiving PERJETA alone were fever, chills, feeling tired, headache, weakness, allergic reactions, and vomiting

Severe allergic reactions: Some people receiving PERJETA may have severe allergic reactions, called hypersensitivity reactions or anaphylaxis. This reaction may be severe, may happen quickly, and may affect many areas of the body

How will my doctor and I know if PERJETA is right for me?

PERJETA has only been shown to work in people with HER2-positive breast cancer. You must have a HER2 test to know if your breast cancer is HER2-positive before receiving an anti-HER2 treatment, such as PERJETA.

What are the most common side effects?

The most common side effects of PERJETA when given with Herceptin and docetaxel for treatment of breast cancer that has spread to other parts of the body (metastatic) are:

Diarrhea

Hair loss

Low levels of white blood cells with or without a fever

Nausea

Feeling tired

Rash

Damage to the nerves (numbness, tingling, pain in hands/feet)

The most common side effects of PERJETA when given with Herceptin and docetaxel as part of an early breast cancer regimen before surgery are:

Hair loss

Diarrhea

Nausea

Low levels of white blood cells with or without a fever

The most common side effects of PERJETA when given with Herceptin and docetaxel following 3 cycles of epirubicin, cyclophosphamide, and fluorouracil as part of an early breast cancer regimen before surgery are:

Feeling tired

Hair loss

Diarrhea

Nausea

Vomiting

Low levels of white blood cells with or without a fever

The most common side effects of PERJETA when given with Herceptin, docetaxel, and carboplatin as part of an early breast cancer regimen before surgery are:

Feeling tired

Hair loss

Diarrhea

Nausea

Vomiting

Low levels of white blood cells with or without a fever

Low platelet count

Low levels of red blood cells

You are encouraged to report side effects to Genentech and the FDA. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Who is KADCYLA for?

KADCYLA® is approved to treat HER2-positive breast cancer that has spread to other parts of the body (metastatic breast cancer) after prior treatment with trastuzumab (Herceptin) and a taxane. Prior treatment could have been for the initial treatment of breast cancer or for the treatment of cancer that had spread to other parts of the body.

Hear it pronounced

Important Safety Information

What is the most important safety information I should know about KADCYLA?

KADCYLA is not the same medicine as trastuzumab (Herceptin).

Liver problems

KADCYLA may cause severe liver problems that can be life-threatening. Symptoms of liver problems may include vomiting, nausea, eating disorder (anorexia), yellowing of the skin (jaundice), stomach pain, dark urine, or itching

Heart problems

KADCYLA may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure). Symptoms may include swelling of the ankles or legs, shortness of breath, cough, rapid weight gain of greater than 5 lbs in less than 24 hours, dizziness or loss of consciousness, or irregular heartbeat

Pregnancy

Receiving KADCYLA during pregnancy can result in the death of an unborn baby and birth defects. Birth control should be used while you receive KADCYLA and for 6 months after your last dose of KADCYLA

If you are exposed to KADCYLA during pregnancy, contact your healthcare provider right away; you are also encouraged to enroll in the MotHER Pregnancy Registry by calling 1-800-690-6720

If you are a mother who is breastfeeding, you should talk with your doctor about either stopping breastfeeding or stopping KADCYLA

Contact your doctor right away if you experience symptoms associated with these side effects.

What are the additional possible serious side effects of KADCYLA?

Lung problems

KADCYLA may cause lung problems, including inflammation of the lung tissue, which can be life-threatening. Signs of lung problems may include trouble breathing, cough, tiredness, and fluid in the lungs

Infusion-related reactions

Symptoms of an infusion-related reaction may include one or more of the following: the skin getting hot or red (flushing), chills, fever, trouble breathing, low blood pressure, wheezing, tightening of the muscles in the chest around the airways, or a fast heartbeat. Your doctor will monitor you for infusion-related reactions

Serious Bleeding

KADCYLA can cause life-threatening bleeding. Taking KADCYLA with other medications used to thin your blood (antiplatelet) or prevent blood clots (anticoagulation) can increase your risk of bleeding. Your doctor should provide additional monitoring if you are taking one of these other drugs while on KADCYLA. Life-threatening bleeding may also happen with KADCYLA even when blood thinners are not also being taken

Low platelet count

Low platelet count may happen during treatment with KADCYLA. Platelets help your blood to clot. Signs of low platelets may include easy bruising, bleeding, and prolonged bleeding from cuts. In mild cases there may not be any symptoms

Nerve damage

Symptoms may include numbness and tingling, burning or sharp pain, sensitivity to touch, lack of coordination, muscle weakness, or loss of muscle function

Skin reactions around the infusion site

KADCYLA may leak from the vein or needle and cause reactions such as redness, tenderness, skin irritation, or pain or swelling at the infusion site. If this happens, it is more likely to happen within 24 hours of the infusion

How will my doctor know if KADCYLA is right for me?

You must have a HER2 test to determine if your cancer is HER2-positive before taking KADCYLA, because benefit has been shown only in patients whose tumors are HER2-positive.

What are the most common side effects of KADCYLA?

The most common side effects seen in people taking KADCYLA are:

Tiredness

Nausea

Pain that affects the bones, muscles, ligaments, and tendons

Bleeding

Low platelet count

Headache

Liver problems

Constipation

Nosebleeds

You are encouraged to report side effects to Genentech and the FDA. You may contact Genentech by calling 1-888-835-2555. You may contact the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.